Gastric epithelial cells differentiate throughout the third postnatal week in rats, and become completely functional by weaning time. When suckling is interrupted by early weaning (EW), cell proliferation and differentiation change in the gastric mucosa, and regulatory mechanisms might involve corticosterone activity. Here we used EW and RU486 (glucocorticoid receptor antagonist) to investigate the roles of corticosterone on differentiation of mucous neck (MNC) and zymogenic cells (ZC) in rats, and to evaluate whether effects persisted in young adults. MNC give rise to ZC, and mucin 6, Mist1, pepsinogen a5 and pepsinogen C are produced to characterize these cells. We found that in pups, EW augmented the expression of mucins, Mist1 and pepsinogen C at mRNA and protein levels, and it changed the number of MNC and ZC. Corticosterone regulated pepsinogen C expression, and MNC and ZC distributions. Further, the changes on MNC population and pepsinogen C were maintained until early- adult life. Therefore, by using EW as a model for altered corticosterone activity in rats, we demonstrated that the differentiation of secretory epithelial cells is sensitive to the type of nutrient in the lumen. Moreover, this environmental perception activates corticosterone to change maturation and reprogram cellular functions in adulthood.